The HPA axis produces what kind of stress response(s) using what neurotransmitter? Where is cortisol from?
- short term & long term stress responses using cortisol
- cortisol from PVN hypothalamus nucleus
Where does corticotrophin releasing hormone/factor get transported from and to where? What does it stimulate the release of from where? What do these hormone levels determine?
- CRH gets transported down portal vessel to ant. pit.
- stimulates release of ACTH & b-endorphin from ant. pit. cells
- these levels determine stress
- CRH release patterns partly determined by early life events
What is co-released with CRH from PVN? What is it good for? When is it up regulated?
- vasopressin (VP) is co-released w/CRH from PVN
- VP helps CRH trigger release of ACTH from ant. pit.
- VP potential is up-regulated in chronic stress situations
What is adrenocorticotropic (ACTH) hormone derived from? What does ATCH trigger the release of?
- ACTH comes from pro-opimelanocortin protein (POMC)
- ACTH triggers release of glucocorticoids from adrenal cortex
Where is coritsol derived from? What does long term stress cause in terms of a neurotransmitter? What does it cause to happen with the adrenal cortex?
- cortisol is from cholesterol
- long term stress causes long term ACTH stimulation which upregulates adrenal cortex= hyperplasia & hypertrophy of gland= more cortisol
What are the permissive actions of cortisol in terms of levels, when it occurs and glucose? Suppressive?
- permissive: low levels, initially, amplifies NE-glucagon pathway via MR= more glucose
- suppressive: higher levels, later, terminates defensive rxns activated by stress
What are the metabolic actions of cortisol? (muscle, protein & carb breakdown?)
-glucose via gluconeogenesis in liver, proteolysis in muscle, lymphoid, skin & CT & lipolysis of adipose
Excess cortisol manifests as what physically? blood sugar for ex.
-high blood sugar, insulin resistance in fat & muscle (NIDDM), protein loss, wasting of muscle, bone matrix & lymphoid tissue, fat accumulation in abdomen, base of neck, face
What is cortisols role in immune system fxn? What do low levels allow? What do high levels cause the release of and therefore cause?
- regulates inflammation & immunity
- low cortisol= permissive
- higher levels= resolves inflammation by reducing release of histamine, bradykinin, PGE & leukotrienes, vasodilating & phagocytosis; limits response by reducing cytokine release, Ab formation, cellular immunity & fever
What system regulates the PVN? What other brain structure is used to regulate the PVN and what neurotransmitter is used? Is cortisol largely excitatory or inhibitory?
- limbic system (PFC, amyg, hippo) via BNST/BST and GABA
- corticol control largely inhibitory
Do CRH neurons stimulate complex stress behavior and ACTH release? What does stress activate in terms of CRH neurons? The CRH acting in the mPFC exerts what stimuli on HPA via what?
-Yes!
-Stress activates CRH neurons in PF/cingulate cortex for anticipation & cognition
-CRH acting in mPFC exerts excitatory influence on HPA via amyg
amyg & BNST for emotional aspects of responses & memory
What is the amyg & BNST for? hypothalamus? PAG, raphe, & LC? all in relation to limbic control of the HPA axis
- amyg & BNST= emotional aspects of responses
- hypo= descending pain control & motivation & drive
- PAG, raphe, LC= mediate behavioral, adrenergic & serotonergic parts of stress
Is stressful stimuli always real? If no, what else can it be and what will it produce?
- No, stimuli can be real or anticipated
- Anticipated stimuli will elicit a reactive & anticipatory HPA response
What are reactive responses and what will they require? How are they conveyed and what do they generate through what structures?
- physiological stressors that will require homeostatic adaptation
- conveyed by sensory pathways & generate reactive stress responses through hypo & pit. (NOT limbic system)
In anticipatory reactions what does the HPA alter in order to do what? Do these processes occur in the presence or absence of a physiological challenge? Is reactive-anticipatory distinction experience independent or experience dependent?
- HPA alters cognitive & emotional processes in order to adapt
- occur in absence of physiological challenge (cortisol response in anticipation rather than reaction to something)
- reactive-anticipatory distinction is experience dependent
With cortisol feedback what happens to HPA activation following stress and why is this necessary? Where does cortisol feed back on in general and why do we have this feed back? Where does cortisol specifically feed back on?
- termination of HPA axis activation following exposure to stress necessary so can limit cortisol & prevent damage
- cortisol does negative feedback on HPA axis= maintain homeostatic level of cortisol release & terminate stress responses
- feeds back specifically on PVN, pituitary, hippo, amyg & mPFC
In rapid feed back cortisol binds to _____ in ____ & _____ cells inhibits _____ & _____ release following ______ stress.
In rapid feed back cortisol binds to GR in PVN & pit. cells inhibit ACTH & cortisol release following acute stress
GR receptors be altered by cortisol feedback by releasing what hormones & neuromodulation of what axis? What is hypercortisolism? What conditions have hypercortisolism? What is hypocortisolism? What conditions have hypocortisolism?
- stressors activate NE, DA, & 5HT neuromodulation of HPA= CRH & VP syn.
- hypercortisolism (cortisol resistance): high levels of cortisol, decreased negative feedback= increased ACTH & cortisol production= hypercortisolism (chronic pain, depression & anorexia)
- hypocortisolism= supersensitivity of GR= increase cortisol feedback= inhibit HPA (fibromyalgia, PTSD, chronic fatigue syndrome)
What two receptors does cortisol react to/with?
binds to mineralcorticoid (MR) & glucocorticoid receptors (GR)
What does MR maintain with hippocampal neurons with what kind of info? What does this lead to? What does MR maintain with HPA and permit during when?
- maintains excitability of hippo neurons to sensory & cortical info= sensitivity to stress for learning & adaptive behavior
- maintains basal activity of HPA & permits increases in cortisol release during onset of stress
Do GRs have high or low affinity for cortisol? What level does there need to be for its activation? What do high levels of cortisol in later stress do the GRs and what does this lead to?
- low affinity for cortisol
- only activated w/high levels of stress (cortisol)
- higher levels of cortisol later in stress response= inhibition of stress response
